This invention relates to a biocompatible, osteogenic, collagen conjugate material, particularly in the form of a sponge, and to a process for making this material. While individual components of this system are known in the art and in the related literature, described herein is a novel composite material, specifically designed to induce osteogenesis within its porous structure, completely biocompatible and non-inflammatory, and ultimately resorbed and replaced by calcified, hard tissue.
Collagen was chosen as the binding matrix and main structural component of the novel graft material herein described for several reasons:
(1) Reconstituted collagen has demonstrated excellent histocapatibility without antibody formation or graft rejection in numerous in vivo implantation studies.
(2) Reconstituted collagen can be fabricated into porous sponge-like structures which allow unimpeded cellular ingrowth.
(3) Collagen is the natural biomaterial which constitutes from 50 to 70% by weight of the bone organic matrix.
(4) Reconstituted collagen has demonstrated the ability to bind both large and small molecular weight macromolecules and complexation with collagen protects these macromolecules from denaturation due to environmental influences, such as glutaraldehyde cross-linking or the effect of other chemical agents; see M. Chvapil et al, International Review of Connective Tissue Research, Vol. 6, (1973), pp. 1-55; S. R. Jefferies et al, Journal of Biomedical Materials Research, Vol. 12 (1978), pp. 491-503; and U.S. Pat. No. 3,843,446.
Sterile collagen products having a felt or fleece-like structure with open, communicating voids between the fibers and used as an absorbent in wounds and bone cavities are described in U.S. Pat. No. 4,066,083.
In 1931, Huggins (Arch. Surg., 22:377-408) reported that proliferating mucosa of Kidney, ureter, or bladder induced bone formation when implanted in connective tissue. This was the first reported experimental model of induced ectopic osteogenesis. More recently, Urist (Science, 150: 893-899, 1965) and Reddi et al (Proc. Natl. Acad. Sci. U.S.A., 69: 1601-1605, 1972) demonstrated that osteogenesis could also be induced by the devitalized, demineralized matrix of bone or dentin. It has been shown that physical factors, including surface charge and geometry of the matrix, are involved, Reddi et al (Proc. Natl. Acad. Sci. U.S.A., 69: 1601-1605, 1972). There is evidence that a soluble factor from demineralized bone, bone morphogenetic protein, is osteo-inductive; see Urist et al, Proc. Natl. Acad. Sci. U.S.A., 76: 1828-1932, 1979.
In 1899, Senn showed healing of experimental canine calverial defects and of human tibial and femoral defects with decalcified ovine bone. Others have shown bone formation in periapical areas in dogs and monkeys and in skull defects in rats after implantation or demineralized bone by itself. The osteogenic potential of demineralized bone powder has been demonstrated in cranial osseous defects in rats. More recently, Mulliken reported on the use of demineralized bone segments, chips, and powder for reconstruction of craniofacial defents in rats and humans; see Mulliken et al. Plast. Reconstr. Surg., 65: 533-559, 1980 and Glowacki et al, Lancet, May 2, 1981, 963-966.
Histomorphometric evaluation of osteogenesis induced by equal masses of demineralized bone powders of various particle sizes, ranging from less than 75 millimicrons to greater than 450 millimicrons, has revealed that smaller particles induced more bone per field, that is the ratio of bone area to implant area, than did larger particles. It has also been noted in the literature that large blocks of demineralized cortical bone induce only a thin layer of new bone on their surfaces. Osteogenesis proceeds more slowly in response to blocks than to powders.
Although blocks, chips, and powders of demineralized bone by itself may be useful for repair of bony defects, a more defined, better designed material is needed to improve the clinical usefulness of induced osteogenesis. Greater control is required over the chemical composition of the graft material than previously accomplished. Banked bone taken from cadavers for demineralization (allogenic bone) must be harvested under rigid standards and conditions to prevent possible immunologic complications or possible transmission of viral or bacterial pathogens. Gamma radiation, one method for sterilization of demineralized bone, may alter the physio-chemical properties critical for bone induction. It is recognized that irradiation of demineralized bone powder before implantation weakens the osteogenic response by 20%.